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Masaru Murai

Publications and source records attributed to Masaru Murai.

At least 73 records · Page 4Linked to original sources
PubMed2003

Elevated Akt activation and its impact on clinicopathological features of renal cell carcinoma.

PURPOSE: Akt has been implicated in the pathogenesis and progression of numerous human malignant tumors because Akt regulates many key effector molecules involved in controlling the balance of survival and apoptosis. Elevated Akt activation has been demonstrated in various types of malignant tumors. In the current study we evaluated Akt activation in renal cell carcinoma and investigated its association with pathological features and clinical outcome. MATERIALS AND METHODS: Akt activation was evaluated by immunohistochemistry using antiphospho-specific Akt antibody, which recognizes only activated Akt, in 48 patients with renal cell carcinoma. High immunostaining tumors were defined as tumors with increased staining intensity compared with adjacent nonneoplastic kidney tissue and low immunostaining tumors were defined as tumors with equivalent or decreased staining intensity. The association of Akt activation status with clinicopathological features was analyzed. RESULTS: Of 48 patients examined 18 (37.5%) demonstrated high antiphospho-specific Akt immunostaining compared with adjacent nonneoplastic kidney tissue, while 30 (62.5%) demonstrated low immunostaining. Elevated immunostaining was significantly associated with tumor grade (p = 0.0354) and metastatic disease (p = 0.0044), while it was not associated with tumor stage or histological subtype. In addition, high antiphospho-specific Akt immunostaining was significantly associated with a poor cancer specific survival rate on univariate analysis (p = 0.0109) but not on multivariate analysis. CONCLUSIONS: Elevated Akt activation could be a common finding, especially in high grade tumor and metastatic disease. It could have an important role in the pathogenesis and progression of renal cell carcinoma.

Adult↗
PubMed2003

Prognostic implication of microvascular invasion in biochemical failure in patients treated with radical prostatectomy.

INTRODUCTION: Micrometastasis before radical prostatectomy (RP) is considered to be related to the biochemical failure after surgery in patients with prostate cancer. To predict the biochemical failure, we evaluated microvascular (lymphatic/vascular) invasion and other pathological findings as prognostic factors for biochemical failure after RP. MATERIALS AND METHODS: Eighty-two men who underwent RPs and received neither preoperative nor postoperative adjuvant therapy were analyzed. Pathological findings of each patient were carefully reviewed to determine pathological factors predicting biochemical failure. The influence of pathological findings on the biochemical failure was evaluated. RESULTS: The overall biochemically assessed disease-free survival rate was 55.7% at 3 years. By univariate analysis, Gleason sum, capsular penetration, and microvascular invasion were significantly associated with the rate of biochemical failure. Microvascular invasion was strongly correlated with Gleason sum, capsular penetration, surgical margin, perineural invasion, and pathological stage. By multivariate analysis, Gleason sum, capsular penetration, and microvascular invasion were independent predictors of biochemical failure. CONCLUSION: This study suggests that in addition to Gleason grade and capsular penetration, microvascular invasion is one of independent prognostic factors in patients with prostate cancer treated with RPs.

Aged↗
PubMed2003

Antitumor effect of a novel nuclear factor-kappa B activation inhibitor in bladder cancer cells.

Nuclear factor (NF)-kappaB is a transcription factor that not only induces and controls various genes, including those of inflammatory cytokines, but also activates genes which suppress apoptosis. It has been clearly demonstrated that certain advanced human bladder cancer cells constitutively acquire the ability to activate NF-kappaB, which not only protects cancer cells from apoptotic cell death, but also upregulates the production of various cytokines that may increase the malignant potential of the disease and cause paraneoplastic syndromes. The NF-kappaB inhibitors may therefore be useful as anticancer agents. An NF-kappaB function inhibitor, a dehydroxymethyl derivative of epoxyquinomicin C (DHMEQ), has recently been designed and synthesized. The effectiveness of DHMEQ against advanced human bladder cancer cell line KU-19-19, in which NF-kappaB is constitutively activated, has been investigated. The DNA-binding activity of NF-kappaB was completely inhibited following 2-6-h exposure to 10 microg/ml of DHMEQ. Marked levels of apoptosis were observed 48 h after DHMEQ administration. These results confirmed that NF-kappaB activation maintains the viability of KU-19-19 cells, that DHMEQ inhibited constitutively activated NF-kappaB, and, consequently, apoptosis was induced. However, it was still possible that DHMEQ caused apoptotic cell death through some other mechanism which has not yet been fully investigated. The authors conclude that DHMEQ could represent a new treatment strategy against advanced bladder cancer.

Animals↗
PubMed2003

Increased activation of CCAAT/enhancer binding protein-beta correlates with the invasiveness of renal cell carcinoma.

Positive inflammatory reactions in an aggressive phenotype are typical features of renal cell carcinoma (RCC). Although a high blood level of inflammatory cytokines, such as interleukin-6, interleukin-8, and tumor necrosis factor-alpha, has been observed in these patients, the mechanisms underlying this clinical phenomenon remain to be elucidated. CCAAT/enhancer binding protein (C/EBP) family are transcription factors which play a role in cell differentiation and inflammatory reactions. Among these, C/EBP-beta induces a variety of cytokines and thus may play a role in the pathogenesis of RCC. We studied the activation of C/EBP-beta determined by electrophoretic mobility shift assay in nine RCC cell lines and 44 tissue samples. Six cell lines showed an activation of C/EBP-beta, whereas three cell lines did not, and two of these three had no expression at all of C/EBP-beta protein. Of 44 tissue samples, 12 (27.3%) showed a >200% increase in the activity compared with the corresponding normal kidney tissues. Locally advanced cases had a significantly higher rate of increased C/EBP-beta activity (5 of 8 = 62.5% in advanced cases versus 7 of 36 = 19.4% in localized cases). Especially, all four cases with renal vein invasion had an increased C/EBP-beta activity. These data suggest that the increased activation of C/EBP-beta may contribute to promote tumor invasiveness and render a malignant phenotype of RCC, although it needs to be validated in a larger series.

Adult↗
PubMed2003

The 2nd conference on Asian trends in prostate cancer hormone therapy.

Among the aims of the 2nd Conference on Asian Trends in Prostate Cancer Hormone Therapy, Hong Kong, December 7-8, 2002, was to lay the groundwork for eventually having cooperative or collaborative studies of prostate cancer specifically in Asian patients. The conference was divided into 2 sessions. In the first session, entitled "Current Status of Therapy for Prostate Cancer in Asian Countries," the results of analysis of 100 patients with prostate cancer enrolled in the Patients Registration System is each of the 6 participating Asian countries were discussed. The Patients Registration System is a database template established by the Japanese Urological Association that allows physicians to compare prostate cancer therapy in the different Asian countries. Session 2 was devoted to a "Roundtable Discussion on the Establishment of Asian Guidelines for Prostate Cancer." This session included 2 lively discussions, on whether Asian physicians can apply Western clinical data to Asian patients, and the need for Asian clinical data and developing clinical trials in the region, respectively.

Androgen Antagonists↗
PubMed2003

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2001). I. Susceptibility distribution].

The bacterial strains isolated from patients diagnosed as having urinary tract infections (UTIs) in 10 institutions in Japan were supplied between the period of September and December 2001. Then, the susceptibilities of them to a variety of antimicrobial agents were investigated. The number of them were 496 strains. The breakdown of these strains was Gram-positive bacteria as 29.6% and Gram-negative bacteria as 70.4%. Susceptibilities of these bacteria to antimicrobial agents were as follows; against Staphylococcus aureus, vancomycin (VCM) showed a strong activity, and this drug also had a strong activity against MRSA in preventing growth of all strains at 1 microgram/mL. In addition, arbekacin (ABK) showed strong activity with the MIC90 of 2 micrograms/mL against MRSA and prevented growth of all strains at 4 micrograms/mL. ABK also showed a strong activity against Staphylococcus epidermidis in preventing growth of all strains at 0.5 microgram/mL. Ampicillin (ABPC) and cefozopran (CZOP) showed a relatively strong activity against S. epidermidis (MIC90: 8 micrograms/mL). ABPC, imipenem (IPM), and VCM showed strong activities against Enterococcus faecalis. No increase of low-susceptible strains in E. faecalis was observed against these antimicrobial agents. Against Escherichia coli, carbapenems showed the highest activities: meropenem (MEPM) prevented growth of all strains at 0.25 microgram/mL; IPM prevented growth of all strains at 0.5 microgram/mL. CZOP and cefotiam (CTM) also showed strong activities against E. coli: MIC90 of CZOP was within 0.125 microgram/mL; MIC90 of CTM was within 0.5 microgram/mL. Quinolone-resistant E. coli was detected at frequency of 9.3%, which was lower than that in the last year, and was higher level than those in up to 1999. MEPM showed the strongest activity against Citrobacter freundii in preventing growth of all strains at 0.125 microgram/mL. Almost all drugs showed strong activities against Klebsiella pneumoniae and Proteus mirabilis, and MEPM prevented growth of all strains within 0.125 microgram/mL. Against Serratia marcescens, the MIC90 of gentamicin (GM) was the lowest value being 2 micrograms/mL, and those of IPM and carumonam were 8 and 16 micrograms/mL, respectively. Against Pseudomonas aeruginosa, almost all drugs were not so active. The MIC90 of GM was 8 micrograms/mL, those of IPM and amikacin were 16 micrograms/mL, and those of all other drugs were over than 32 micrograms/mL.

Anti-Bacterial Agents↗
PubMed2003

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2001). II. Background of patients].

Five-hundred thirty one bacterial strains isolated from 412 patients diagnosed as having urinary tract infections (UTIs) in 10 institutions in Japan were supplied between September and December 2001. Then, the clinical background of patients were investigated such as sex, age, and type of infections, infections and kind of bacteria, frequency of bacteria isolation by age and infections, bacteria and infections by timing of antibiotics administration, and bacteria and infections by surgical procedures. With regard to the relationship between age and sex of patients and type of infections, the number of cases aged lower than 50 years was few and complicated UTIs without indwelling catheter was the most frequent in male patients. In females, the number of patients aged lower than 20 years was few. Most of female patients aged lower than 80 years had uncomplicated UTIs. As for the relationship between type of infections and kind of bacteria, Escherichia coli decreased as the infections were more complicated, and Pseudomonas aeruginosa and Enterococcus faecalis increased as the infections were more complicated. In relation of these results to age of patients, isolation frequency of E. coli gradually decreased with aging in patients aged 20 years and older with uncomplicated UTIs. The isolation frequencies of E. faecalis decreased with aging in the patients with complicated UTIs without indwelling catheter while P. aeruginosa decreased with aging in the patients with complicated UTIs with indwelling catheter. E. coli was isolated a few after administration of antibiotics, and P. aeruginosa and E. faecalis were frequently isolated after administration in the patients with all types of infections. As for type of causative organisms in UTIs and with or without surgical operation, E. coli was frequently isolated in the patients without surgery in the patients with uncomplicated UTIs and complicated UTIs without indwelling catheter, while P. aeruginosa was frequently isolated in the patients who underwent surgery in the patients with uncomplicated UTIs and complicated UTIs with indwelling catheter. In uncomplicated UTIs, isolation frequencies of Klebsiella spp., P. aeruginosa, and E. faecalis were significant in the patients with surgery. In complicated UTIs without indwelling catheter, Klebsiella spp. was frequently isolated in the patients with surgery. In complicated UTIs with indwelling catheter, S. aureus and Staphylococcus spp. were frequently isolated in the patients without surgery.

Adolescent↗
PubMed2003

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (2001). III. Secular changes in susceptibility].

The bacteria (Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa) isolated from patients diagnosed as urinary tract infections (UTIs) in 10 institutions in Japan were supplied between September and December, 2001. Then, the susceptibilities of these bacteria to various antimicrobial agents were examined, and the results were compared with those obtained between 1992 and 2000. Comparison was made by classifying strains isolated from patients into those in uncomplicated UTIs and those in complicated UTIs (including with or without indwelling catheter). The drug sensitivity of S. aureus in this year was comparable to those in up to the previous year, and S. aureus showed the best susceptibility to vancomycin (VCM). E. faecalis showed good susceptibility to ampicillin and imipenem, and the MIC90s were 2 micrograms/mL. The susceptibility of E. faecalis to VCM was also good. E. coli showed good susceptibility to the drugs except penicillins. Among cephems, the susceptibility to cefozopran (CZOP) was better (MIC90: < or = 0.125 microgram/mL). Just as the last report, the decreases in susceptibility of E. coli to quinolones were also observed in the patients with complicated UTIs. The susceptibility of Klebsiella spp. to all the test drugs did not significantly change in 2001 and was generally good but not to penicillins. Among cephems, Klebsiella spp. showed good susceptibility to flomoxef, cefpirome, cefixime, and CZOP with < or = 0.125 microgram/mL of MIC90s either in uncomplicated or complicated UTIs. Although the drug sensitivity of P. aeruginosa was generally low, the detection of the strains that showed good susceptibility to quinolones and carbapenems (MIC: < or = 0.125-2 micrograms/mL) were relatively frequent.

Anti-Bacterial Agents↗
PubMed2002

Clinical value of prostate specific antigen based parameters for the detection of prostate cancer on repeat biopsy: the usefulness of complexed prostate specific antigen adjusted for transition zone volume.

PURPOSE: To our knowledge the indications for repeat prostate needle biopsy in men whose previous transrectal ultrasound guided biopsy results revealed no evidence of cancer have not yet been defined. We identified the most effective method for detecting prostate cancer on repeat biopsy. MATERIALS AND METHODS: One or more systematic repeat prostate biopsies were performed in 144 consecutive patients, including 86 with prostate specific antigen (PSA) levels between 4 and 10 ng./ml. at repeat biopsy. Men in whom cancer was detected on repeat biopsies were compared with their counterparts in terms of digital rectal examination findings, PSA based parameters and an atypical prostate on initial prostate biopsy. RESULTS: Prostate cancer was detected on repeat biopsy in 39 of the 144 patients and in 19 on subset analysis of 86. Serum PSA levels at repeat biopsy did not differ significantly in patients with and without prostate cancer. According to receiver operating characteristics analysis the alpha1-antichymotrypsin-PSA complex adjusted for transition zone volume had the greatest area under the curve values, that is 0.756 for all 144 patients and 0.768 for the subset analysis of 86. Multiple logistic regression analysis of the subset of 86 patients showed that alpha1-antichymotrypsin-PSA complex adjusted for transition zone volume was the only significant independent predictor of cancer. CONCLUSIONS: alpha1-Antichymotrypsin-PSA complex adjusted for transition zone volume was the most powerful predictor of cancer in men who had undergone previous negative prostate biopsies. This parameter may be used to avoid more unnecessary repeat biopsies with an acceptable decrease in sensitivity.

Aged↗
PubMed2002

SN-38 induces cell cycle arrest and apoptosis in human testicular cancer.

OBJECTIVE: CPT-11 is one of the most widely used camptothecin analogues and is converted to form the active metabolite SN-38. Clinical trials are ongoing to better characterize its spectra of clinical activity, to determine the optimal schedules of administration, and to define the usage in combination with other chemotherapeutic compounds. MATERIALS AND METHODS: KU-MT, an AFP-producing testicular carcinoma cell line, was exposed to SN-38, etoposide, or cisplatin for 24 h, and the resulting cytotoxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazonium bromide (MTT) assay. This paper describes the effects of SN-38 on the cell proliferation and cell cycle of testicular tumor cells in culture. RESULTS: SN-38 was shown to inhibit KU-MT cell growth more potently than either etoposide or cisplatin. A marked decrease in the percentage of S phase cells was accompanied by the enhancement of cyclin E levels. In concentrations of >30 nmol/l, SN-38 arrested the cell cycle in G2 and induced cell death via apoptosis. The apoptosis was promoted by Bax and p53 protein, which were both shown to be present by flow cytometric and Western blot analyses. CONCLUSION: These results suggest that CPT-11, a pro-drug of SN-38, may be clinically useful for the treatment of testicular cancer, and that the mechanism of this agent's cytotoxicity consists of cell cycle arrest and concomitant apoptosis.

Antineoplastic Agents, Phytogenic↗
PubMed2002

Laparoscopic adrenalectomy: current status with a review of Japanese literature.

A decade has elapsed since laparoscopic adrenalectomy was first performed in 1992. Accumulated experiences of laparoscopic adrenalectomy have shown superior results to treat small functional benign tumors and make the indication expand to large tumors, pheochromocytomas and localized malignant tumors. Following the initially established transperitoneal approach, which includes anterior and lateral approaches, the retroperitoneal lateral flank and posterior lumber approaches have been performed. Each approach has advantages and disadvantages. The transperitoneal approach supplies a large operative field, many anatomical landmarks and easy handling. But it causes post-operative irritability and it is very difficult to perform after previous upper abdominal surgery. The retroperitoneal approach can be performed even after previous abdominal surgery and patients may be more comfortable after the operation. However, the narrow working space and the lack of anatomical landmarks may increase the rate of intra-operative complications and the rate of conversion to open surgery. Although there is no clear preference between transperitoneal and retroperitoneal approaches, the transperitoneal approach is commonly employed and the transperitoneal anterior approach seems to be the easiest one for right adrenal tumors and the transperitoneal lateral approach for left adrenal tumors. The shorter convalescence with laparoscopic adrenalectomy as compared with open adrenalectomy has been accepted and lower morbidity from laparoscopic adrenalectomy has been achieved. The operative time has been shortened to the level of open adrenalectomy. Less blood loss, less pain and better cosmesis are absolute advantages for the patients. Laparoscopic adrenalectomy is now the gold standard for the treatment of adrenal tumors.

Adrenalectomy↗
PubMed2002

Long-term effects of transurethral microwave thermotherapy.

BACKGROUND: To identify the clinical valuables predicting a favorable outcome after transurethral microwave thermotherapy (TUMT) of the prostate with Prostatron. METHODS: One hundred and two patients with lower urinary symptoms were treated with TUMT using a Prostatron device with the low-energy protocol (Prostasoft version 2.0 J). The pre-operative subjective score and objective voiding parameters were collected from the medical record. To test the differences in the risk of the necessity for additional treatments for several subgroups, Kaplan-Meier survival analyses and log-rank tests were used. RESULTS: The Kaplan-Meier analyses showed that 67% of the patients received additional treatment within five years. The median period for receiving additional treatment was 37 months. The patients with a peak flow rate greater than 6.5 mL per second, with a urethral length less than 40 mm, or with an age over 64 years all demonstrated a significantly longer period before receiving additional treatment, when compared with their counterparts. These three factors were also significant in multivariate analysis to predict the long-term outcome. CONCLUSIONS: Overall durability of TUMT was limited. Aged patients with a relatively high peak flow rate or with a short prostatic urethral length resulted in lower risk of receiving additional treatments after TUMT.

Aged↗
PubMed2002

Significance and diagnostic accuracy of renal calculi found by ultrasonography in patients with asymptomatic microscopic hematuria.

BACKGROUND: The purpose of the present study was to evaluate the clinical significance and the accuracy of the diagnosis of renal calculi incidentally found by ultrasonography (US). METHODS: A total of 906 subjects (639 men and 267 women) aged 18-78 years were referred for asymptomatic microscopic hematuria. Of these, 743 patients who underwent US were studied. RESULTS: Hyperechogenic spots in the central echo complex suggesting renal calculi were noted in 195 patients (21.5%). The occurrence of hyperechogenic spots was higher in patients with 20 or more urinary red blood cells per high-power field (chi(2) = 4.896, P = 0.0269) and in men than in women (chi(2) = 7.101, P = 0.0077), but it was lowest in patients who were 29 years old or younger. Of these 195 patients, who were followed up for 1-161 months (average: 33.5 months), 24 patients (12.3%) needed urological management. Extracorporeal shockwave lithotripsy was carried out in eight patients, transureteral lithotripsy was carried out in three patients, spontaneous passage occurred in 11 patients and medication for hyperuricemia was initiated in two patients (1%). Among the patients in whom hyperechogenic spots were found on the kidney by US but calculi were not visible on abdominal plain radiographs, 39 patients underwent computed tomography. Of them, 31 patients were confirmed to have renal calculi. CONCLUSION: The obtained results suggest that US is an effective and reliable means of detecting renal calculi in patients with asymptomatic microscopic hematuria, and in facilitating prompt urological intervention or predicting the natural course of renal calculi.

Adult↗
PubMed2002

STAT3, but not ERKs, mediates the IL-6-induced proliferation of renal cancer cells, ACHN and 769P.

BACKGROUND: Although interleukin-6 (IL-6) has been suggested to function as an autocrine growth factor in renal cell carcinoma (RCC), the underlying mechanism responsible for the IL-6-induced proliferation of RCC has not been defined. The aim of this study was to characterize the signaling cascades mediating IL-6-induced proliferation and to investigate the use of effective novel interventions to block the IL-6-induced autocrine growth of renal cancer cells. METHODS: IL-6-induced proliferation and intracellular signaling cascades were analyzed in four human renal cancer cell lines Caki-1, ACHN, 769P and A498. IL-6-induced activation of STAT3 (signal transducer and activator of transcription-1) and extracellular signal-regulated kinases (ERKs), and the effects of anti-IL-6 neutralizing antibody, Jak inhibitor AG 490, and MEK1 inhibitor PD 98059 were analyzed by Western blotting using phospho-specific antibodies. The DNA-binding activities of STATs were analyzed by EMSA. Apoptosis was determined by using nuclear staining and the TUNEL assay. Changes in the apoptosis-related proteins, bcl-2, bcl-xL, and bax were analyzed by Western blotting. RESULTS: IL-6 induced tyrosine phosphorylation and increased the DNA binding activity of STAT3 and, to a lesser extent, STAT1 in all cell lines except for Caki-1, which did not express the IL-6 receptor subunit gp130. ERKs were constitutively activated in all cell lines and the activation level was not up-regulated further by exogenously added IL-6 nor down-regulated by anti-IL-6 neutralizing antibody. IL-6-induced STAT3 tyrosine phosphorylation and DNA binding activity was inhibited by treatment with Jak specific inhibitor AG 490; however, it was not affected by the MEK1 inhibitor PD 98059. Moreover, treatment with AG 490 inhibited IL-6-induced proliferation of ACHN and 769P cells and induced apoptosis with the down-regulation of bcl-2 and the up-regulation of bax. CONCLUSIONS: This study identified STAT3, but not ERKs, to be a major mediator of IL-6-induced proliferation of renal cancer cells. Although ERKs were constitutively activated, ERKs were not found to be essential for the IL-6-induced proliferation and modulation of the STAT3 activity. Because the Jak specific inhibitor AG 490 effectively inhibited the IL-6-induced STAT3 activity and induced apoptosis, the blockade of the STAT3 signaling pathways is considered to be potentially useful as a novel therapeutic approach for RCC.

Antibodies, Monoclonal↗
PubMed2002

Hypercalcemia and acute renal failure caused by production of parathyroid hormone-related protein from renal cell carcinoma.

A 69-year-old male patient was diagnosed with right-sided renal cell carcinoma and humoral hypercalcemia of malignancy caused by an excessive production of parathyroid hormone-related protein. The hypercalcemia led to acute tubular necrosis, so the patient had to be put on hemodialysis. The renal failure was accompanied by hyponatremic encephalopathy. Rapid correction of the hyponatremia might have initiated central pontine myelinolysis.

Acute Kidney Injury↗
PubMed2002

Bcl-2 and androgen receptor gene expression in androgen-independent subclone derived from mouse androgen-dependent cells.

We investigated bcl-2 and androgen receptor (AR) expression in an androgen-independent subline derived from mouse androgen-dependent mammary carcinoma cells. The androgen-independent SCAI cells were subcloned by cultivating androgen-dependent SC2G cells in serum-free, androgen-free conditions. The growth of the SCAI cells was not affected by testosterone. Western blot analysis showed greater expression of Bcl-2 protein in SCAI cells than in SC2G cells. A four-day culture with 4 microM antisense oligonucleotide complementary to mouse bcl-2 significantly decreased the viability of SCAI cells, when compared with sense control. The amount of the AR-mRNA expression in SCAI cells was slightly weaker. Direct sequence analysis showed no mutations in the AR of either androgen-dependent or -independent cells. These data indicate that the increased expression of Bcl-2 protein plays an important role in acquiring tolerance for the testosterone ablation, although it is not related to AR gene alteration.

Androgens↗